This study is a first-in-human (FIH), Phase 1, multicenter, open-label study to evaluate the safety, tolerability, and PK of IGM-7354 in participants with relapsed and/or refractory tumors. The study design consists of a dose-escalation stage and dose-expansion stage. Study participation will consist of a 28-day screening period, a treatment period, and a safety follow-up period 90-days after the last dose.

开始日期2023-01-10

申办/合作机构

IGM Biosciences, Inc.

100 项与 IGM-7354 相关的临床结果

登录后查看更多信息

100 项与 IGM-7354 相关的转化医学

登录后查看更多信息

100 项与 IGM-7354 相关的专利（医药）

登录后查看更多信息

项与 IGM-7354 相关的文献（医药）

Cancer Immunology Research

IGM-7354, an Immunocytokine with IL15 Fused to an Anti–PD-L1 IgM, Induces NK and CD8+ T cell–Mediated Cytotoxicity of PD-L1–Positive Tumor Cells

Article

作者: Desbois, Mélanie ; Denson, Carolyn R. ; Giffon, Thierry ; Keyt, Bruce A. ; Sekar, Keerthana ; Calhoun, Susan E. ; Kotturi, Maya F. ; Wang, Beatrice T. ; Pandey, Sivani ; Sinclair, Angus M. ; Saini, Avneesh K. ; Ng, Dean ; Yakkundi, Poonam ; Santos, Daniel ; Hart, Kevin C. ; Logronio, Kathryn

Abstract:

IgM antibodies are preformed pentameric or hexameric molecules that can be engineered to generate high-affinity and high-avidity fully human antibody therapeutics. In this study, we report an immunocytokine, IGM-7354, which was designed to bind multiple PD-L1 receptors while trans-presenting a single IL15/IL15Rα complex on the joining chain to IL15Rβγ-expressing cytotoxic NK and CD8+ T cells. We evaluated the pharmacologic and antitumor properties of IGM-7354 in preclinical models. IGM-7354 induced potent proliferation of NK and CD8+ T cells, both in vitro using healthy human peripheral blood mononuclear cells and in vivo in humanized mice, through the IL15/IL15Rα complex. In a mixed-lymphocyte reaction assay with exhausted human T cells, IGM-7354 restored the secretion of IFNγ compared with the IL15/IL15Rα complex or anti–PD-L1 alone, suggesting a rescue of exhausted T cells in vitro. Robust single-agent activity was observed in the humanized PD-L1+ MDA-MB-231 breast cancer mouse model. Antitumor responses were enhanced by adding IGM-7354 to the anti-CD38 daratumumab in RPMI-8226 multiple myeloma or anti-CD19 chimeric antigen receptor T-cell therapies in Raji lymphoma models. Finally, in cynomolgus monkeys, pharmacodynamic activity of increased NK and CD8+ T-cell proliferation was observed in multiple tissue compartments. Taken together, this study demonstrates the feasibility of developing a safe and effective IgM-based immunocytokine for the treatment of cancer, exploiting the multivalency of an IgM antibody to bind PD-L1 with high affinity and avidity and stimulate NK and CD8+ T-cell effectors.

项与 IGM-7354 相关的新闻（医药）

2025-07-01

·EndPoints

Kevin Tang's Concentra snags another buyout, this time for IGM Biosciences

Kevin Tang is on a hot streak. Concentra Biosciences, the shell company from his hedge fund Tang Capital, has secured its fourth buyout of a struggling biotech so far in 2025. This time, Concentra is taking out IGM Biosciences, the California biotech that had once inked a $6 billion biobucks pact with Sanofi but saw that deal halved in 2024 , its oncology ambitions wither , and its pivot to autoimmune diseases short-lived . The move for IGM comes after Concentra’s successful takeouts of Elevation Oncology , Kronos Bio and Allakos . It did not succeed on Acelyrin, though, as the California immunology drug developer stuck to its merger with Alumis . The buyouts have taken place amid a surge in restructurings and shutterings in the biotech industry, as many companies have had to pull back on their ambitions due to dwindling investor support and/or clinical setbacks. For IGM, the deal concludes a nearly six-month process. After devoting just a few months to an autoimmune disease turnaround attempt, IGM flashed the red lights in early January, saying it would let go of most of its staff and search for strategic alternatives. Now, the Mountain View-based biotech said it’s exiting to Concentra for $1.24 per share $IGMS in cash. The company’s stock price was up about 16% in early Tuesday trading, slightly surpassing the buyout price. IGM’s board “unanimously determined” that the Concentra deal is “in the best interests of all IGM Biosciences stockholders,” per a Tuesday release. The company said the deal comes with the right to get 100% of the closing net cash in excess of $82 million. The company had $183.8 million in cash and investments at the end of 2024. Shareholders could also get 80% of the net proceeds from any sale of IGM’s product candidates and IP within one year post-closing. According to an SEC filing , these assets have the potential to be offloaded:

并购

2023-12-07

·佰傲谷BioValley

裁员22%，砍掉所有血液瘤管线

裁员、砍管线是资金困难的生物药企活下去最经常采用的办法。近日，总部位于美国加州的IGM Biosciences决定裁员22%，并且停止所有血液瘤项目以及其靶向细胞因子候选产品的临床开发。IGM预计通过裁员和管线消减可以将公司现金流从原来坚持到2025年下半年延长到2026年第二季度。根据美国证券交易委员会（SEC）的文件，截至2023年9月30日，IGM拥有290名全职员工。IGM首席执行官表示，虽然公司停止的项目临床和临床前的数据表现都很亮眼，但是鉴于公司在资本市场融资困难，日子越来越难过，只能决定集中资源在最可能在近期产生效益的项目上。押注实体瘤和自免IGM表示将和赛诺菲继续合作，一起开发肿瘤学、免疫学和炎症候选药物。集中资源开发其治疗结直肠癌的IgM死亡受体5（DR5）激动剂抗体，以及用于自身免疫性疾病的IgMT细胞接合抗体。死亡受体5（DR5）激动剂Aplitabart联合FOLFIRI和贝伐珠单抗治疗二线转移性结直肠癌的随机临床试验正在招募患者，目标是到2024年第一季度末招募约110名患者。除了美国的临床试验地点外，该试验还包括亚洲和欧洲的多个临床试验地点。Aplitabart在晚期结直肠癌患者中应用的单臂联合临床试验也正在进行中。预计在2024年上半年完成10mg/kg Aplitabart和FOLFIRI治疗后期结直肠癌的患者入组。Aplitabart联合FOLFIRI治疗的一组患者报告的1期数据显示，其安全性与单独化疗的预期安全性大致相当。剂量为3mg/kg的Aplitabart和不含贝伐珠单抗的FOLFIRI的组合在24例患者组中的中位无进展生存期（PFS）为5.6个月，高于标准护理三线结直肠癌治疗（不含贝伐珠单抗）约2个月的历史中位无进展生存期。该组观察到的最长无进展生存期已超过16个月，且多位患者使用Aplitabart和FOLFIRI的治疗持续时间比之前的FOLFIRI方案更长。与此同时，IGM将优先推进imvotamab的临床开发，这是一种基于IgM的CD20xCD3双特异性T细胞结合抗体，用于自身免疫性疾病。关于imvotamab目前正在进行两项1b期临床试验，一项用于严重系统性红斑狼疮（SLE），另一项用于严重类风湿性关节炎（RA）。这些临床试验正在扩大到包括多个美国和国际临床试验地点。最近IGM还获得了FDA的批准，批准了其使用imvotamab治疗特发性炎症性肌病（肌炎）的IND申请，并且正在准备推进该临床试验。在临床前体内研究中，imvotamab已证明组织内的深部B细胞耗竭，其中致病性免疫细胞的耗竭可能对自身免疫性疾病的长期临床益处至关重要。Imvotamab还在临床前体外研究中证明，与利妥昔单抗相比，它可以更有效地消耗CD20表达水平低的B细胞。此外，IGM还划提交IND，以开始IGM-2644的临床开发，IGM-2644是一种CD38xCD3T细胞接合抗体，正在研究用于治疗自身免疫性疾病。亏损扩大，裁员缩管线2023年11月14日，IGM发布Q3财报，2023财年前三财季累计收入147.90万美元，去年同期累计收入为69.70万美元，同比增长112.20%。2023财年前三财季累计净亏损1.86亿美元，去年同期累计净亏损为1.69亿美元，同比扩大10.20%。作为公司战略重整的一部分，IGM将停止所有血液肿瘤学临床开发以及其靶向细胞因子候选产品的临床开发。包括Aplitabart联合birinapant用于治疗急性髓系白血病；IGM-2644（CD38xCD3）治疗多发性骨髓瘤；以及IGM-2537（CD123xCD3）和IGM-7354（IL-15xPD-L1）。去年11月，IGM在2022年美国血液学会（ASH）年会上，以海报的形式展示了几款候选药物在血液瘤中的临床前数据。数据显示与传统IgG抗CD38抗体相比，IgM-2644具有更强的补体依赖性细胞毒性(CDC)活性，此外，IGM-2644以最小的细胞因子释放实现了对达雷妥尤单抗耐药细胞系的强效T细胞依赖性细胞毒性（TDCC）杀伤，以及对骨髓瘤患者样本的强效TDCC杀伤。在人源化异种移植模型中，IGM-2644 也被证明可以抑制CD38+肿瘤生长，且与IgG双特异性T 细胞接合剂相比，它避免了杀死免疫效应细胞。IgM-2537在细胞因子释放最少的情况下显示有效的体外和体内活性。IGM-2537 被证明与人 CD123 结合具有高亲和力和特异性。IGM-2537 与CD123和CD3抗原共同参与，导致T细胞重定向杀伤急性髓系白血病（AML）细胞系，同时伴随 T 细胞活化，并在离体测定中以生理相关的效应/靶标比率消除AML原始细胞。与 IgGT细胞接合分子相比，IGM-2537还显示出显着减少的细胞因子释放，例如IFN-γ、TNF-α和IL-6。虽然数据鼓舞人心，但是资金的缺乏加上创新药物的开发需要的超额预算让IGM不得不放弃血液瘤管线。值得注意的是，IGM去年和赛诺菲刚刚达成巨额交易。2022年3月29日，赛诺菲和IGM达成超过60亿美元的合作协议。根据协议，双方将利用IGM公司独有的IgM抗体技术平台，开发针对3个肿瘤学靶点和3个免疫学/炎症靶点的激动剂。IGM公司将获得1.5亿美元的前期付款，在开发、监管和商业里程碑方面的总金额可能超过60亿美元。针对每个肿瘤学靶点，IGM公司可能获得高达9.4亿美元的里程碑付款；在免疫学/炎症领域，针对每个靶点，IGM公司有资格获得高达10.65亿美元的里程碑付款。在血液瘤方面管线的缩减，可能会影响到赛诺菲给予的里程碑付款。参考来源：1.https://endpts.com/igm-biosciences-cuts-22-of-workforce-axes-hematologic-oncology-program/2.https://www.globenewswire.com/news-release/2023/12/05/2791338/0/en/IGM-Biosciences-Announces-Strategic-Pipeline-Prioritization-and-Cash-Runway-Extension.html3.https://investor.igmbio.com/news-releases/news-release-details/igm-biosciences-presents-data-t-cell-engager-portfolio本周好文推荐如需转载请联系佰傲谷并在醒目位置注明出处﹀ ···

临床申请

2023-12-06

·FierceBiotech

IGM, with cash dipping below $390M, cuts headcount 22%, stops blood cancer work to stretch money

IGM ended September with 290 full-time employees. How much money does a biotech need to feel comfortable in today’s market? IGM Biosciences added to evidence that the number is big after the market closed Tuesday, when it revealed a 22% reduction in its headcount and prioritization of its pipeline to make the hundreds of millions in its bank go further. Talking at an investor event last month, IGM CEO Fred Schwarzer gave an upbeat answer to a question about the biotech’s financial footing, telling attendees that it had “plenty of cash to get through into the second half of 2025.” The cash pile stood at $387 million at the end of September. Yet, while IGM has a bank balance to turn some biotechs green with envy, it has decided it needs to cut costs. IGM ended September with 290 full-time employees. The decision to reduce that figure by 22% is part of a set of changes intended to keep IGM going into the second quarter of 2026. Through the changes, IGM is focusing its resources on colorectal cancer and autoimmune diseases. The biotech is halting work on two assets, the CD123xCD3 bispecific IGM-2537 and IL-15xPD-L1 candidate IGM-7354, and cutting the list of the indications targeted by two other molecules. Work on aplitabart in acute myeloid leukemia and in combination with birinapant is stopping, as is development of IGM-2644 in multiple myeloma. In a statement, Schwarzer said IGM is “very encouraged by the clinical and preclinical data that we have generated for the programs” but is halting work in response to “the difficult conditions in the capital markets for our industry.” The changes are intended to narrow IGM’s focus on opportunities with “the most potential to produce significant near-term value,” the CEO said. IGM will continue to study aplitabart, a DR5 agonist, in colorectal cancer, forging toward the goal of enrolling 110 patients in a randomized trial by the end of the first quarter of next year. Development of the CD38xCD3 bispecific IGM-2644 is continuing in autoimmune diseases. IGM aims to file to test the drug candidate in humans next year. Work on the CD20xCD3 bispecific imvotamab is continuing too.

蛋白降解靶向嵌合体财报

100 项与 IGM-7354 相关的药物交易

登录后查看更多信息

研发状态

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
局部晚期恶性实体瘤	临床1期	美国	IGM Biosciences, Inc.	2023-01-10
复发癌	临床1期	美国	IGM Biosciences, Inc.	2023-01-10
复发性实体肿瘤	临床1期	美国	IGM Biosciences, Inc.	2023-01-10
血液肿瘤	临床前	美国	IGM Biosciences, Inc.	2020-03-25